Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome

Sebastião Freitas de Medeiros; MárciaMarlyWinck Yamamoto; JamillyAparecida Vicente Jacomeli; José Maria Soares Junior; Gustavo Arantes Rosa Maciel; Edmund Chada Baracat

doi:doi:10.11648/j.jgo.20261403.12

Research Article |

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Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome

Sebastião Freitas de Medeiros^*

, MárciaMarlyWinck Yamamoto

, JamillyAparecida Vicente Jacomeli

, José Maria Soares Junior

, Gustavo Arantes Rosa Maciel

, Edmund Chada Baracat

Published in Journal of Gynecology and Obstetrics (Volume 14, Issue 3)

Received: 19 February 2026 Accepted: 18 March 2026 Published: 11 July 2026

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Abstract

This comprehensive review focuses on the relevance of hyperinsulinemia in women with polycystic ovary syndrome (PCOS). It highlights the most robust scientific evidence on the management of this condition within the context of PCOS. A systematic search of studies published in English language was conducted using Google Scholar, PubMed, and Cochrane databases. Keywords used alone or combined with “PCOS” included: hyperinsulinemia, incretin hormones, and dipeptidyl peptidase-4. The search strategy was complemented by manual review of references from selected articles. Glucagon-like peptide-1 receptor agonist and glucagon-dependent insulin tropic polypeptide provide various metabolic beneficial effects in addition to the weight loss. Dipeptidyl peptidase-4 inhibitors, expressed by various cells, prevent GLP-1 degradation and decreases insulin signaling in different cells, particularly in hepatocytes, and adipocytes. Regarding the management of hyperinsulinemia, the review suggests that incretin hormone agonist and dipeptidyl peptidase-4 inhibitors may represent favorable therapeutic options for addressing insulin resistance in women with PCOS, particularly those with obesity. However, this review does not explore dietary interventions and physical activity as primary strategies for managing dysglycemia in this population.

Published in	Journal of Gynecology and Obstetrics (Volume 14, Issue 3)
DOI	10.11648/j.jgo.20261403.12
Page(s)	75-85
Creative Commons	This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.
Copyright	Copyright © The Author(s), 2026. Published by Science Publishing Group

Keywords

Polycystic Ovary Syndrome, Hyperinsulinism, Incretin Hormone, Dipeptylpeptidase

1. Introduction

In adults, PCOS has been defined by the presence of oligoanovulation, clinical and/or biochemical hyperandrogenism, and polycystic ovary morphology (PCOM) and/or ovarian volume >10cm³

[1]

. In adolescents, despite the use of ultrasound has not been recommended, nevertheless the recommendation is based only on opinion of specialists as practical points, not in scientific evidences

[2]

. For that reason the results must be considered with certain reserve. The prevalence of polycystic ovary syndrome (PCOS) ranges from 3% to 11% in adolescents and from 5% to 20% in adults, according to diagnostic criteria and population studied

[3, 4]

. Although PCOS was recently renamed to polyendocrine metabolic ovarian syndrome (PMOS), in this review, the PCOS abbreviation will be maintained without affecting the review's conclusions. [5]. The most prevalent characteristic of PCOS is increased ovarian androgen production, found in over 75% of patients, and increased adrenal androgens can be found in about 20% - 30%

[6]

. Regarding androgens, either from adrenal or ovarian sources, there have been attempts to translate basic knowledge into clinical practice

[6]

. It is already clear that the biochemical hyperandrogenism increases the risk of central obesity, dysfunctional and hypertropic adipocytes, dyslipidemia, impaired fasting glucose (IFG), glucose intolerance (GI), low-grade chronic inflammation, and hyperinsulinemia

[7]

. Additionally, hyperinsulinemia may stimulate the ovarian synthesis of androstenedione and testosterone

[7-9]

Considering the leading role of the hyperandrogenism in the development of comorbidities, such as central obesity and hyperinsulism, in women with PCOS, the clinical management needs to be based on different phenotypes of PCOS since individual characteristics must tailor the finest treatment choice

[10]

. It must be highlighted however that some procedures are applied to all PCOS phenotypes

[11]

. Insulin regulates plasma glucose homeostasis and acts indifferent tissues such as ovarian cells, liver, skeletal muscle, and adipose tissue. Insulin resistance, common in PCOS, determines various metabolic dysfunctions linked to an increased risk of cardiovascular disease (CVD)

[12]

. As dysglicemia can be present in 50%- 70% of women with PCOS, the present review is focused in the pharmacological management of hyperinsulinism/ hyperinsulinemia in these patients.

2. Definition of Hyperinsulinemia/Insulin Resistance in Women with PCOS

Hyperinsulinemia may be either a cause or a consequence of hyperandrogenemia

[9, 13, 14]

. As mentioned before, hyperinsulinemia itself may induce an increase in androgen levels

[8, 9]

. On the other side, hyperandrogenism may promote central obesity, dysfunctional adipocytes, impaired fasting glucose (IFG), glucose intolerance (GI) and insulin resistance (IR) with elevated circulating insulin levels

[9, 13]

. Increased levels of insulin in women with PCOS vary with the phenotype and are reported in over 65% of patients

[15]

. Insulin inhibits liver synthesis of sex hormone binding globulin (SHBG) and insulin- like growth fator-1 (IGF-1) and a decrease in SHBG results in increased free testosterone levels, a predictive marker of insulin resistance

[16, 17]

Table 1. Recommended cut-offs and ranges commonly used for diagnosing insulin resistance/hy.

Parameter	Cut offs	Ranges	References
SHBG(nmol/l)	20	20-37	Chen et al, 2021
			Jayagopal et al, 2003
			Nadaraja et al, 2018
Baseline insulin (pmol/l)	85	68-105	McAuley et al, 2001
			Lewandowsky et al, 2019
			Lee et al, 2003
HOMA-IR	2.2	1.8-3.8	De Medeiros et al, 2017
			Lewandowsky et al, 2019
			Gayoso-Diz et al, 2013
			Abdesselan et al, 2021
Quicki	0.357	0.310-0.360	Martins et al, 2007
			Kartz et al, 2000
			Park et al, 2021

SHBG=sex hormone binding globulin

HOMAR-IR=homeostatic model assessment of insulin resistance.

Quicki=quantitative insulin sensitivity check index

Clinically, the presence of hyperinsulinemia is identified by the presence of acanthosis nigricans (AN) in about 30%- 68% of patients

[18, 19]

and skin tags in nearly 16%

[20]

. The laboratorial diagnosis of hyperinsulinemia might be performed with baseline levels of insulin over 12.2 µUI/ml (85 pmol/l)

[21, 22]

. Moreover, different published cut-offs for hyperinsulinemia (IR) are shown in Table 1 [21-32]. IR in adipose tissue and skeletal muscle may be diagnosed using the Homeostatic Model Assessment-IR (HOMA-IR), the Quantitative Insulin Sensitivity Check Index (QUICKI test) or many other biochemical and validated anthropometric biomarkers

[26, 33]

2.1. Highlights on Treatment of Hyperinsulinemia/Insulin Resistance in PCOS

Any treatment for insulin resistance and/or hyperinsulinemia in women with PCOS should be prescribed only after a precise diagnosis of this condition. Initially, lifestyle and diet could be prescribed to nearly all women with PCOS. Various new drugs have been demonstrated to be an adequate treatment for women with PCOS with IR (Figure 1). The present review will be limited to the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs), glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) inhibitors (Table 1), particularly recommended in obese PCOS

[34, 35]

. Incretins are the gut secreted hormones GIP and GLP-1

[34, 36]

. The GLP-1 is synthesized by post-translational processing of glucagon in the epithelial L-cells of the intestine, particularly in the ileum and colon that are in contact with nutrients

[37]

Download: Download full-size image

Figure 1. Dipeptidyl peptidase-4 and incretins use in polycystic ovary syndrome.

Table 1. Current therapy approaches for management of hyperinsulinemia/ insulin resistance in obese women with PCOS.

Glucagon-like peptídeo-1 receptor agonist (GLP-1 RA)

Exenatide

Liraglutide

Semaglutide

Dipeptidyl peptidase-4 (DDP-4) inhibitors

Sitagliptin

Alogliptin

Sexagliptin

GLP-1 RA and GIP synergic activities

Tirzepatide

2.2. Glucagon-Like Peptide-1 Receptor Agonist

The GLP-1 RAs, mimic incretin GLP-1 secreted by L-cells of distal intestine, bind to insulin receptors on pancreatic β-cells, stimulate insulin secretion, expand pancreatic β-cells through growth, differentiation and proliferation via activation of epidermal growth factor receptor

[37]

. Additionally, they reduce glucagon secretion and exhibit anti-inflammatory properties

[37]

. Nutrient ingestion, mainly glucose and fat are the primary physiological stimulus for L-cell to secret GLP-1, as soon as 15-30 min after ameal

[37]

. In clinical practice, GLP-1 RA, are adequate alternative to the use of metformin, it does not increase the risk of hypoglycemia and has shown significant improvement in insulin action, weight reduction, waist circumference reduction and reproductive function with increased pregnancy rates

[38, 39]

. Nowadays various studies indicate the effectively of GLP-1 RAs in the treatment of women with PCOS

[34]	Abdalla MA, Deshmukh H, Atkin S, et al. The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence. Therap Advan Endocrinol Metab. 2021; 12: 1-16.
[40]	Bader S, Bhatti R, Abusanana S. A systematic review of GLP-1on anthropometric PCOS. Women’s Health. 2024; 20. https://doi.org/10.1177/17455057241234530 View Article
[41]	Morais BAAH, Prizão VM, Souza MM, et al. The efficacy and safety of GLP-1 agonists in PCOS women living with obesity in promoting weight loss and hormonal regulation: A meta-analysis of randomized controlled trials. J Diab Complicat. 2024; 30(10): 108834.
[42]	Rahim S, Pergolizzi J. The potential role of glucagon-like peptide-1 (GLP-1) agonist for polycystic ovary syndrome. Cureus. 2025; 17(1): e77998. https://doi.org/10.7759/cureus.77998 View Article
[43]	Xing C, Li C, He B. Insulin sensitizers for improving the endocrine and metabolic profile in overweight women with PCOS. J Clin Endocrinol Metab.2020; 105(9): 2950-2963.
[44]	Lin S, Deng Y, Huang J, et al. Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials. Sci Rep. 2025; 15(1): 16512. https://doi.org/10.1038/s41598-025-99622-4 View Article
[45]	Srinivasan D, Lofton HF. Effect of GLP-1 agonists on weight loss in patients with polycystic ovary syndrome and obesity: A single-center study. Obesi Pillars. 2022; 2: 100016
[46]	Alhomoud IS, Wheeler SE, Dixon DL. Repurposing incretin therapies: a narrative review of emerging indications across cardiometabolic, liver, kidney, neurological, psychiatric, and other systems. Can J Physiol Pharmacol. 2025; 103(9): 298-311. https://doi.org/10.1139/cjpp-2025-0038 View Article
[47]	Bu T, Su Z, Pan Y, et al. Glucagon-like peptide-1: New regulator in lipid metabolism. Diabetes Metab J. 2024; 48(3): 354-372.
[48]	Mullur N, Morissette A, Morrow NM, et al. GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms. J Endocrino. 2024; 263: e240046.
[49]	Szczesnowicz A, Szeliga A, Niwczyk O, et al. Do GLP-1 analogs have a place in the tratment of PCOS? New insights and promising therapies. J Clin Med. 2023; 13(18): 5915.

[34, 40-49]

Currently, a few types of GLP-1 RAs are approved for treatment of dysglycemia and insulin resistance in overweight or obese women with PCOS; particularly exenatide, liraglutide, dulaglutide and semaglutide. Furthermore, they can be associated with metformin or other oral hypoglycemic drugs

[50]

. In their action GLP-1 RAs suppress appetite (central anorexic effect) at hypothalamic level by increasing the electrical activity in the pro-opiomelanocortin (POMC) neurons

[43, 46]

, help to decrease central obesity by activated protein kinase (AMPK) in the centro medial hypothalamic nucleus, reducing body weight

[50, 51]

, improve glycemic control by increasing insulin sensitivity in peripheral tissues and glucose uptake

[49, 50]

, and decline the inflammation state by reducing macrophages secretion of proinflammatory cytokines

[40, 49] (Figure 2)

. Moreover, GLP-1 RAs reduce glucagon secretion; reduce metabolic disorders associated fatty liver disease (MASLD) and visceral adipose tissue

[40, 49]

. After oral glucose tolerance test (OGTT) in women with PCOS it was observed increase in GIP and lower GLP-1 concentrations. GLP-1 is also reduced in impaired glucose tolerance (ITG), impaired fasting glucose (IFG) and dyslipidemic states

[47]

. In total, GLP-1RAS exhibit a cardio protective effect

[48]

Download: Download full-size image

Figure 2. Integrated pathways: GLP-1 RAs in the treatment of PCOS.

The first GLP-1RA exenatide, approved for clinical use in 2005, has a short half-life of 2.4 hours and immediate effect

[52]

. For clinical use, it is available in two preparations: a short action formulation for subcutaneous (SC) administrations twice daily (BID) before meals and a long acting formulation given weekly, containing exenatide dispersed in microspheres to be released via biodegradation in three stages: 48 hours, 2 weeks, and approximately 7 weeks. With a dosevarying between 5 µg- 10µg, SC, (BID) in women with PCOS for 24 weeks, exenatide promoted weight loss, reduced fat mass, reduced body mass index (BMI) and waist circumference (WC)

[53, 54]

. Regarding weight loss it was shown to be superior to metformin

[53, 54]

. Additionally, it improved lipid profile, hepatocyte IR, glucose concentration, decreased glycated hemoglobin (HbA1C), decrease HOMA-IR, decrease C-reactive protein (CRP), and improved p- selectin and e-selectin accepted biomarkers of CVD

[52-57]

. Exenatide promotes benefic metabolic changes and diminishes the risk of CVD

[58]

. Adverse events related to exenatide are of low intensity and frequency, being common nausea, vomiting, diarrhea, nasopharingite and headache with respect to hormone levels, exenatide (10µg) increases SHBG (24%), decreases total testosterone level (17%), and increases the number of menstrual cycles. However, in other study, with 20 µg/day, exenatide did not modify the levels of total testosterone (T), androstenedione (A4), dehydroepiandrostenone (DHEA), and SHBG

[53-57]

Liraglutide given once a day, at doses ranging from 0.6 mg to 1.8 mg, delays gastric emptying, controls appetite and reduces body weight

[59-62]

. In a study including women with PCOS, liraglutide, given at a daily dose of 1.8 mg, for 26 weeks, reduced body weight (5%), decreased liver fat mass (44%), decreased body fat mass (19%) and decreased visceral adipose tissue

[45, 62]

. Yet, in other study, also enrolling women with PCOS, liraglutide given for 6 months, promoted more than 5% loss in body weight, with total body loss of 4-6 kg

[61]

. Body weight loss of 5.2 kg to 9.1 kg, BMI loss of 1.9kg, WC decrease of 4.1 cm was also showed in PCOS

[38, 60, 61]

. Because some inconsistent results, it is currently recommended to increase liraglutide dose to 3 mg daily in overweight/obese women with PCOS

[61]

. Liraglutide, at doses of 1.2 to 3.0 mg daily has been shown to increase luteinizing hormone (LH), follicle-stimulating hormone (FSH), SHBG, and decrease total T, A4, and DHEAS

[61]

. Regarding menstrual cycles length the current results remain inconsistent

[61]

In preclinical study, examining a DHEA induced PCOS female rats, dulaglutide was shown to decrease insulin with significant reduction in T and increased of SHBG levels, when compared with no treated rats. Additionally, the ovarian gene expressions of 3B-HSD, CYP (19α1), and STAR were decreased after three weeks of treatment

[62, 63]

. Recent studies have considered the effects of dulaglutide in women with PCOS

[43, 62, 64]

. Dulaglutide is a once weekly GLP-1 RA that may ameliorate adherence

[65]

. It is used at a weekly dose of 1.5 mg by subcutaneous injection

[65]

. Combined with caloric-restricted diet (CRD) of 1.000-1.300 kcal day dulaglutide was recently used in overweight/obese adult women with PCOS

[66]

. This initial study did not show significant differences in menstrual cycles and anthropometric measures when compared with the use of CRD alone. However, during six months of treatment a 7% loss of weight took a shorten time

[66]

Regarding metabolic biomarkers, dulaglutide associated with CRD significantly decreases fasting glucose and HbA1C levels without clear benefits in lipids, hormones, liver function biomarkers, and C-reactive protein (CRP). About body composition, no different was observed in visceral adipose tissue (VAT) with the addition of dulaglutide to CRD in women with PCOS [67]. No difference in lean body mass (LBM) was also observed. The decrease in systolic (SBP) and diastolic blood pressures (DBP) was similar between use isolated of CRD or of a combination of CRD with dulaglutide. With different intensities, adverse events have been reported in about 37% of users of dulaglutide; mainly gastrointestinal reactions such us nausea, vomiting, constipation, diarrhea, abdominal distension, dyspepsia, and loss of appetite. These adverse events tend to ameliorate after three/ four weeks of use

[66, 67]

and are particularly exacerbated at daily dose of 3.0 mg to 4.5 mg.

Semaglutide, approved by FDA in 2019, is a GLP-1 RA with a long half-life of 7-8 days, was recently used in overweight/obese women with PCOS in a weekly dose of 0.5 mg, subcutaneous

[68]

. It delays gastric emptying in up to four hours

[68]

and has shown the ability of more consistently reduction in body weight, either in diabetic obese subjects

[69-74]

or in women with PCOS

[72]

. The use of 1 mg per week also demonstrated to diminish body weight, BMI, WC, VAT, fasting insulin, and HDL-C

[72, 73]

. When given to women with PCOS, phenotype A, for three months, semaglutide demonstrated ability to decrease body weight over 10%, 7.6±3.0 kg, BMI (↓3.1±1.0kg/m²)

[74]

. When its use was extended to 6 months, body weight loss reached up to 11.5 kg, therefore more than weight loss seen with the use of liraglutide

[75]

It was also reported that some patients might lose less than 5% of body weight, particularly those more obese women and were considered unresponsive to semaglutide even when given for 6 months

[74]

. This observation result suggested the need to increase the doses to 1 mg to 5 mg/weekly

[75]

. Semaglutide was also reported to decrease fasting glucose, fasting insulin, HOMA-IR, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels

[72-76]

. The main reported adverse event of semaglutide was nausea, and to minimize adverse events the dose might gradually be increased from 0.2 to 1 mg every two weeks up to reach 1-2 mg

[72, 73]

. If necessary and well tolerated the dose may be till increased to 2mg-4mg/weekly

[72]

. Regarding hormone levels, semaglutide significantly increased SHBG, decreased both calculated and measured free T

[72]

. Additionally, an oral formulation of semaglutide may be soon introduced in the treatment of PCOS, using a dose of 7 mg once daily. In other conditions such as diabetes mellitus and obesity this oral presentation has been evaluated at doses varying between 30 to 50 mg/day

[76]

. Recently, when associated with metformin in women with type 2 diabetes metabolites (T2DM), cycle length and HOMA-IR were significantly decreased

[76]

. In animal model, semaglutide was shown to alleviate ovary inflammation in PCOS

[73]

. Regarding the effect on the bioavailability of the combined oral contraceptive, the current results remain inconsistent

[77]

2.3. Dipeptidyl Peptidas-4 (DPP-4)

The enzyme DPP-4 (CD26), a glycoprotein protease expressed by various cells, prevents GLP-1 degradation, prolonging its half-life with increased blood levels

[78]

. DPP-4 protease decreases insulin signaling pathways in different cells, including hepatocytes, and adipocytes

[79-81]

. More recently, it was seen that its expression and activity appears to be higher in women with PCOS due to hyperandrogenism

[82, 83]

. Despite these observations at the present time the studies showed inconsistency

[81, 83]

. By reducing GLP-1 degradation, the use of DPP-4 inhibitors, increases the levels of incretions and can be an alternative treatment for insulin resistance/hyperinsulinemia in women with PCOS

[82, 83]

In women with PCOS sitagliptin, a DPP-4 inhibitor, has been used at doses of 100-200 mg daily and adverse events such as abdominal pain, nausea, vomiting, diarrhea are not common

[83]

. The use of sitagliptin in women with PCOS have shown increased GLP-1 levels, increased growth hormone half-life, decreased blood glucose, enhanced insulin secretion, decreased total cholesterol, and decreased VAT in overweight/obese women with PCOS

[82, 83]

. Currently, there is no study with power and time enough regarding weight loss and insulin sensitivity in women with PCOS using DPP-4 receptor inhibitors

[82, 83]

2.4. Glucagon- Dependent Insulin Tropic Polypeptide

GLP-1Randglucose-dependent insulinotropic polypeptide (GIP) synergic activities Tirzepatide, a synthetic peptide with 39 amino acids has a dual agonist effect for GLP-1 and gastric GIP receptors

[84]

. GIP was the first incretin hormone identified in humans

[84]

with potent insulinotropic action

[84, 85]

. Duodend and jejuna mucosas are the primary source of GIP by K-cells

[85]

. Currently, it was approved for treating obese T2DM patients

[86-91]

. Clinical trials in patients with T2DM have demonstrated that its use improves glycemic control and promotes weight loss

[89, 90]

. Terzepatide has a long half-life of about 5 days allowing it to be used once a week

[91, 92]

. In non-PCOS T2DM patients, when used at a dosage of 15mg/weekly for 26 to 40 weeks, tirzepatide was shown to decrease glycated hemoglobin (HbA1C), HOMA-IR, triglycerides (TG) levels and up to 15% of the body weight

[93-95]

. A reduction of 3% to 8% in weight has been reported by other studies

[96]

. Reported adverse events are vomiting, constipation, diarrhea, and abdominal pain. Additionally, it may interact with anti-platelet drugs and by affecting the absorption of oral contraceptives, it may diminish its effectively

[97]

. Because dysglycemia, obesity and metabolic syndrome are common microbiome in women with PCOS, tirzepatide has a potential utility in the treatment of this condition

[97, 98] (Figure 3)

. Further, tirzepatide helps alter the gut microbiome which is beneficial to women with PCOS

[97]

. In a recent trial in women with PCOS, used in combination with metformin a reduction in body weight of about 8 kg in 90% of women was observed

[91]

. More recently, GLP-1 RAs isolated or combined with GIP has shown to be very effective in promoting weight loss and improve dysglycemia and dyslipidemia in women with PCOS

[98-100]

Download: Download full-size image

Figure 3. Mechanistic Pathways and clinical benefits or Tirzepatide in the management of PCOS.

3. Conclusions

Insulin resistance with hyperinsulinemia accompanied of obesity must be considered a crucial aspect for the development of CVD in women with PCOS. It is clearly established that physical activity and hypo caloric diet remain the first-line treatment to all PCOS phenotypes. When needed, various pharmacologic products are available to treat IR and hyperinsulinemia in this population. The use of GLP-1 RAs has demonstrated varying effectiveness in promoting weight loss, decrease in VAT over different time of treatment in women with PCOS. Considering the heterogeneity of PCOS phenotypes, it is needed to tailor an ideal management for individual patients. Women with PCOS and hyperinsulinism in their phenotype may be safety treated with agonists of incretin hormones and dipeptyl-peptidase-4.

Abbreviations

3 B-HSD	3-Beta-hydroxysteroid Dehydrogenase
A4	Androstenediona
AMPK	Activated Protein Kinase
AN	Acanthosis Nigricans
BID	Twice daily
BMI	Body Mass Index
CRD	Calorie-Restricted Diet
CRP	C- Reactive Protein
CVD	Cardiovascular Disease
CYP	Aromatase
DBP	Diastolic Blood Pressure
DHEA	Dehydroepiandrosterone
DHEAS	Dehydroepiandrosterone Sulfate
DPP-4	Dipeptidyl peptidase-4
FDA	Food and Drug Administration
FSH	Follicle-Stimulating Hormone
GI	Glucose Intolerance
GIP	Glucose-dependent Insulinotropic Polypeptide
GLP-1	Glucagon-Like Peptide-1
GPL-1 RA	Glucagon-Like Peptide-1 Receptor Agonist
HbA1C	Glycated Hemoglobin
HDL- C	High-Density Lipoprotein Cholesterol
HOMA-IR	Homeostasis Model Assessment of Insulin Resistance
IFG	Impaired Fasting Glucose
IGF-1	Insulin-like Growth Factor-1
IR	Insulin Resistance
ITG	Impaired Tolerance Glucose
LH	Luteinizing Hormone
MASLD	Metabolic Dysfunction-Associated Steatotic Liver Disease
OGTT	Oral Glucose Tolerance Test
PMOS	Polyendocrine Ovarian Metabolic Syndrome
PCOM	Polycystic Ovary Morphology
PCOS	Polycystic Ovary Syndrome
QUICKI	Quantitative Insulin Sensitivity Check Index
SBP	Systolic Blood Pressure
SC	Subcutaneous
SHBG	Sex Hormone-Binding Globulin
StAR	Steroidogenic Acute Regularoy Protein
T	Total Testosterone
T2DM	Diabetes Mellitus Tipo 2
TG	Triglycerides
VAT	Visceral Adipose Tissue
WC	Waist Circumference

Acknowledgments

The authors acknowledge to American Journal Experts for English revision.

Author Contributions

Sebastião Freitas de Medeiros: Supervision, Conceptualization, Data curation, Formal analysis, Methodology, Writing – original draft, Writing – review & editing

MárciaMarlyWinck Yamamoto: Data curation, Methodology, Formal analysis, Writing – review & editing

JamillyAparecida Vicente Jacomeli: Data curation, methodology, writing – original draft.

José Maria Soares Junior: Formal analysis, Writing – review & editing

Gustavo Arantes Rosa Maciel: Formal analysis, Writing – review & editing

Edmund Chada Baracat: Supervision, Formal analysis, Writing – review & editing

Data Availability Statement

There search data are not publicly available on legal or ethical grounds. In addition, all data produced and analyzed during this study were included in this article. Further inquiries can be directed to the corresponding author.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Teede HJ, Tay CH, Laven J, et al. Recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome. J Clin Endocrinol Metab. 2023; 108(10): 2447-2469. https://doi.org/10.1210/clinem/dgad463
[2]	de Medeiros SF, deMedeiros AKLWY, de Magalhães LF, et al. Fundamentals to diagnosing polycystic ovary syndrome in adolescents: A critical literature review.J Gynecol Obstet. 2024; 12(4): 67-80. https://doi.org/10.11648/j.jgo.20241204.12
[3]	Salari N, Nankali A, Ghanbari A, et al. Global prevalence of polycystic ovary syndrome in women worldwide: a comprehensive systematic review and meta-analysis. Arch Gynecol Obstet. 2024; 310(3): 1303-1314.
[4]	Naz MSG, Therani FR, Majd HA, et al.The prevalence of polycystic ovary syndrome in adolescents: a systematic review and meta-analysis. Int J Reprod Biomed. 2019; 13(8): 533-542.
[5]	Teede, H. J., Khomami, M. B., Morman, R., Laven, J. S. E., Joham, A. E., Costello, M. F., Patil, M., Rees, D. A., Berry, L., Cree, M. G., Zhao, H., Norman, R. J., Dokras, A., Piltonen, T., & Global Name Change Consortium. (2026). Polyendocrine metabolic ovarian syndrome, the new name for polycystic ovary syndrome: a multistep global consensus process. The Lancet, 407, 2329–2339.
[6]	de Medeiros SF, Barbosa BB, de Medeiros MAS, Yamamoto AKLW, Yamamoto MMW. Adrenal androgen predictive effects on clinical and metabolic abnormalities of polycystic ovary syndrome. Rev Bras Ginecol Obstet. 2022; 44(2):142-153. HYPERLINK " https://doi.org/10.1055/s-0041-1741030" \t "_blank" https://doi.org/10.1055/s-0041-1741030
[7]	de Medeiros SF, Rodgers RJ, Norman RJ. Adipocyte and steroidogenic cell crosstalk in polycystic ovary syndrome. Hum Reprod Update. 2021; 27(4):771-796.
[8]	Unluhizarci K, Karaca Z, Kelestimur F. Role of insulin and insulin resistance inandrogen excess disorders. World J Diabetes. 2021; 12(5): 616-629.
[9]	Banu H, Morshed M, Akhtar N, et al. Total testosterone significantly correlates with insulin resistance in polycystic ovary syndrome. Gynecol Reprod Endocrinol Metab. 2021; 2: 106-111. https://doi.org/10.53260/GREM.212027
[10]	Wang T, Zhang T, Wang J, Lu T. Evolving PCOS Management: From Symptom Control to Phenotype-Targeted Therapy. Diabetes Metab Syndr Obes. 2026; 19: 560296.
[11]	Cowan S, Lim S, Alycia C, et al. Lifestyle management in polycystic ovary syndrome-beyond diet and physical activity. BMC Endocr Disord. 2023; 23(1): 14. https://doi.org/10.1186/s12902-022-01208-y
[12]	Wang J, Wu D, Guo H, et al. Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome. Life Sci. 2019; 236: 116940. https://doi.org/10.1016/jfs.2019.116940
[13]	Legro RS. Hyperandrogenism and Hyperinsulinemia. In: Global Library of Women's Medicine. London: GLOWM; 2008. https://doi.org/10.3843/GLOWM.10303
[14]	Chang KJ, Chen JH, Chen KH. The pathophysiological mechanism and clinical treatment of polycystic ovary syndrome: A molecular and cellular review of the literature. Int J Mole Sci. 2024.
[15]	Ding H, Zhang J, Zhang F, et al. Resistance to the insulin and elevated level of androgen: A major cause of polycystic ovary syndrome. Front Endocrionl. 2021; 12: 741764. https://doi.org/10.3389/fendo.2021.741764
[16]	Zhu JL, Chen Z, Feng WJ, et al. Sex hormone-binding globulin and polycystic ovary syndrome. Clin Chim Acta. 2019; 499: 142-148.
[17]	Xing C, Zhang J, Zhao H, et al. Effect of sex hormone-binding globulin on polycystic ovary syndrome: Mechanisms, manifestations, genetics, and treatment. Int J Womens Health. 2022; 14: 91-105. https://doi.org/10.2147/IJWH.S344542
[18]	Videira-Silva A, Albuquerque C, Fonseca H. Acanthosis nigricans as a clinical marker of insulin resistance among overweight adolescents. Ann Pediatr Endocrinol Metab. 2019; 24(2): 99-103.
[19]	Khan B, Basu R. Acanthosis nigricans in adolescents with polycystic ovary syndrome. Int J Reprod Contracept Obstet Gynecol. 2022; 11(3): 765-769.
[20]	Abusailik MA, Muhanna AM, Almuhisen AA, et al. Cutaneous manifestation of polycystic ovary syndrome. Dermatol Reports. 2021; 13(2): 8799. https://doi.org/10.4081/dr.2021.8799
[21]	Lee S, An H, Rhee S, et al. Optimal fasting insulin cutoff value to predict clinical and/or biochemical hyperandrogenism in Korean women with polycystic ovary syndrome. Clin Exp Obstet Gynecol. 2023; 50(1): 238. https://doi.org/10.31083/j.ceog5011238
[22]	Martins WP, Santana LF, Nastri CO, et al. Agreement among insulin sensitivity indexes on the diagnosis of insulin resistance in polycystic ovary syndrome and ovulatory women. Eur J Obstet Gynecol Reprod Biol. 2007; 133(2): 203-207.
[23]	Jayagopal V, Kilpatrick ES, Jennings PE, et al. The biological variation of testosterone and sex hormone-binding globulin (SHBG) in polycystic ovarian syndrome: implications for SHBG as a surrogate marker of insulin resistance. J Clin Endocrinol Metab. 2003; 88(4): 1528-1533.
[24]	Nadaraja RND, Sthaneshwar P, Razali N. Establishing the cut off values of androgen markers in the assessment of polycystic ovarian syndrome. Malays J Pathol. 2018; 40(1): 33-39.
[25]	Chen F, Liao Y, Chen M, et al. Evaluation of the efficacy of sex hormone binding globulin in insulin resistance assessment based on HOMA-R in patients with PCOS. Reprod Sci. 2021; 28(9): 2504-2513.
[26]	Lewandowski KC, Skowronska-Jozwiak E, Ukasiak K, Galuszko K, et al. How much insulin resistance in polycystic ovary syndrome? Comparison of HOMA-IR and insulin resistance (Belfiore) index models. Arch Med Sci. 2019; 15(3): 613-618.
[27]	Katz A, Nambi SS, Mather K, et al. Quantative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. J Clin Endocrinol Metab. 2000; 85(7): 2402-2410.
[28]	Park SY, Gautier JF, Chon S. Assessment of insulin secretion and insulin resistance in human. Diabetes Metab J. 2021; 45(5): 641-654
[29]	Gayoso-Diz P, Otero-Gonzáles A, Rodrigues-Alvarez MX, et al. Insulin resistance (HOMA-IR) cut-off values and the metabolic syndrome in a general adult population: effect o fender and age: EPIRCE cross-sectional study. BMC Endocr Dis. 2013; 13(1): 47. https://doi.org/10.1186/14-6823-13-47
[30]	Abdesselam A, Zidoum H, Zadjali F, et al. Estimate of the HOMAR-IR cut-off value for identifying subjects at risk of insulin resistance using a machine learning approach. Sultan Qaboos Uni Med J. 2021; 21(4): 604-612.
[31]	de Medeiros SF, Ormond CM, de Medeiros MAS, et al. Metabolic and endocrine connections of 17-hydroxypregnenolone in polycystic ovary syndrome women. Endocr Connect. 2017; 6(7): 479-488.
[32]	McAuley KA, Williams SM, Mann JI, Wlaker RJ, Lewis-Barned NJ, Temple LA, Duncan AW. Diagnosing insulin resistance in the general population. Diabetes Care. 2001; 24(3): 460-464.
[33]	Tehrani FN, Fayas M, Firouuzi F, et al. Longitudinal trajectories of insulin resistance in women with polycystic ovary syndrome: A functional data analysia approach. Endocr Connect. 2025; 14(8): e250266. https://doi.org/10.1530/EC-25-0266
[34]	Abdalla MA, Deshmukh H, Atkin S, et al. The potential role of incretin-based therapies for polycystic ovary syndrome: a narrative review of the current evidence. Therap Advan Endocrinol Metab. 2021; 12: 1-16.
[35]	Siamashvili M, Davis SN. Update on the effects of GLP-1 receptor agonists for the treatment of polycystic ovary syndrome. Exp Rev Clin Pharmacol. 2021; 14(9): 1081-1089.
[36]	Ghafari A, Maftoohi M, Samarin ME, et al. The last update on polycystic ovary syndrome (PCOS), diagnosis criteria, and novel treatment. 2025; 17: 100228. https://doi.org/10.1016/j.endmts.2025.100228
[37]	Santos-Hernández M, Reimann F, Gribble FM. Cellular mechanisms of incretin hormone secretion. J Mol Endocrinol. 2024; 72(4): e230112.
[38]	Celik O, Yazici D, Ciudin A, et al. GLP-1receptor analogs: evidence linking to effect on metabolic and reproductive functions in patients with PCOS and obesity. Obs Facts. 2025; 31: 1-15. https://doi.org/10.1159/000547055
[39]	Papaetis GS, Kyriacou A. GLP-1 receptor agonists, polycystic ovary syndrome and reproductive dysfunction: Current research and future horizons. Adv Clin Exp Med. 2022; 31(11): 1265-1274.
[40]	Bader S, Bhatti R, Abusanana S. A systematic review of GLP-1on anthropometric PCOS. Women’s Health. 2024; 20. https://doi.org/10.1177/17455057241234530
[41]	Morais BAAH, Prizão VM, Souza MM, et al. The efficacy and safety of GLP-1 agonists in PCOS women living with obesity in promoting weight loss and hormonal regulation: A meta-analysis of randomized controlled trials. J Diab Complicat. 2024; 30(10): 108834.
[42]	Rahim S, Pergolizzi J. The potential role of glucagon-like peptide-1 (GLP-1) agonist for polycystic ovary syndrome. Cureus. 2025; 17(1): e77998. https://doi.org/10.7759/cureus.77998
[43]	Xing C, Li C, He B. Insulin sensitizers for improving the endocrine and metabolic profile in overweight women with PCOS. J Clin Endocrinol Metab.2020; 105(9): 2950-2963.
[44]	Lin S, Deng Y, Huang J, et al. Efficacy and safety of GLP-1 receptor agonists on weight management and metabolic parameters in PCOS women: a meta-analysis of randomized controlled trials. Sci Rep. 2025; 15(1): 16512. https://doi.org/10.1038/s41598-025-99622-4
[45]	Srinivasan D, Lofton HF. Effect of GLP-1 agonists on weight loss in patients with polycystic ovary syndrome and obesity: A single-center study. Obesi Pillars. 2022; 2: 100016
[46]	Alhomoud IS, Wheeler SE, Dixon DL. Repurposing incretin therapies: a narrative review of emerging indications across cardiometabolic, liver, kidney, neurological, psychiatric, and other systems. Can J Physiol Pharmacol. 2025; 103(9): 298-311. https://doi.org/10.1139/cjpp-2025-0038
[47]	Bu T, Su Z, Pan Y, et al. Glucagon-like peptide-1: New regulator in lipid metabolism. Diabetes Metab J. 2024; 48(3): 354-372.
[48]	Mullur N, Morissette A, Morrow NM, et al. GLP-1 receptor agonist-based therapies and cardiovascular risk: a review of mechanisms. J Endocrino. 2024; 263: e240046.
[49]	Szczesnowicz A, Szeliga A, Niwczyk O, et al. Do GLP-1 analogs have a place in the tratment of PCOS? New insights and promising therapies. J Clin Med. 2023; 13(18): 5915.
[50]	Sridharan K, Sivaramakrishnan G. Expanding therapeutic horizons: glucagon-like peptide-1receptor agonists ando sodium glucose transporte-2 inhibitors in polycystic ovarian syndrome: A comprehensive review including systematic review and network meta-analysis of randomized clinical trials. Diabetol Metab Syndr. 2025; 17(1): 168. https://doi.org/10.1186/s13098-025-01730-8
[51]	Gleason E, Levine L, Lee IT, Koelper N, Amaro A, Dokras A. Effect of glucagon-like peptide 1 receptor agonist medications on weight loss in patients with and whitout polycystic ovary syndrome. Fertil Steril. 2025; 124 (3): 562-564.
[52]	Tang L, Yuan L, Yang G, et al. Changes in whole metabolities after exenatide treatment in overweight/obese polycystic ovary syndrome patients. Clin Endocrinol.2019; 91(4):508-516.
[53]	Ye ZR, Yan CQ, Liao N, et al. The effectiveness and safety of exenatide versus metformin in patients with polycystic ovary syndrome: A meta-analysis of randomized controlled trials. Reprod Sci. 2023; 30(8): 2349-2361.
[54]	Vatankhah A, Jamhiri M, Vatankhah S, et al. Improved ovarian adiponectin system expression in polycystic ovary syndrome treated with exenatide. Clin Exp Reprod Med. 2025; 52(1): 98-100.
[55]	Hu Y, Song X, Hamiti S, et al. Comparison of exenatide alone or combined with metformin versus metformin in treatment of polycystic ovaries: a systematic review and meta-analysis. BMC Endocr Disord. 2023; 23(1): 250. https://doi.org/10.1186/s12902-023-01497
[56]	Bai C, Wang Y, Niu Z, et al. Exatinade improves hepatocyte insulin resistence induced by different regional adipose tissue. Front Endocrinol. 2002; 13: 1012904. https://doi.org/1010.3389/fendo.2022.1012904
[57]	Tang L, Yuan L. Changes in whole metabolities after exenatide treatment in overweight/ obese polycystic ovary syndrome patients. Clin Endocrinol. 20019; 91(4): 508-516.
[58]	Dawson JA. Sathyapalan T, Vince R, et al. The effect of exantide on Cardiovascular risk markers in women with polycystic ovary syndrome. Front Endocrinol. 2019; 10: 189. https://doi.org/10.3389/fendo.2019.00189
[59]	Elkind-Hirsch KE, Chappeell N, Shaler D, et al. Liraglutide 3 mg on weight, body composition and hormonal and metabolic parameters in women with obesity and Polycystic ovary syndrome. A randomized placebo- phase 3 study. Fertil Steril. 2022: 118(2): 371-381.
[60]	Van Can J, Sloth B, Jensen C, et al. Effects of the once-daily GLP-1 analong Liraglutide on gastric emptying glycemin parameters, appetite and energy metabolism obese, non-diabetic adults. Int J Obstet. 2024; 38(6): 784-793.
[61]	Frossing S, Nylander M, Chabanova E, et al. Effect of liraglutide on ectopic fat in polycystic ovary syndrome: A randomized clinical tria. Diabetes Obes Metab. 2018; 20(1): 215-218.
[62]	Wu LM, Wang YX, Zhan Y, Liu AH, Wang YX, Shen HF, Wang YF, Wang LY, Tao ZB, Wang YQ. Dulaglutide, a long-acting GLP-1 receptor agonist, can improve hyperandrogenemia and ovarian function in DHEA-induced PCOS rats. Peptides. 2021; 145: 170624. https://doi.org/10.1016/j.peptides.2021.170624
[63]	Van J, Frias JP, Bonara E, Raha S, et al. Gastrointestinal tolerability of once-weekly dulaglutide 3.0mg and 4.5 mg: A post hoc analysis of the incidence and prevalence of náusea, vomiting and diarrhea in AWARD-11. Diabetes Ther. 2021; 12(10): 2783-2794.
[64]	Bhaskaran D, Angappan S. Targeting Obesity in PCOS: A Review of Current Pharmacological Interventions and Future Directions. CMMB. 2025; 32 (3):229.
[65]	Guo L, Zhang B, Hou J, et al. Evaluation of characteristics of gastrointestinal adverse events with once-weekly dulaglutide treatment in Chinese patients with type 2 diabetes: A post hoc pooled analysis of two randomized trials. Diabetes Ther. 2020; 11(8): 1821-1833.
[66]	Nauck MA, Quast DR, Wefers J, Meler JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes ‘state-of-the-art. Mol Metab. 2021; 46: 101102. https://doi.org/10.1016/j.molmet.2020.101102
[67]	Zhang Y, Qu Z, Lu T, et al. Effects of a dulaglutide plus calorie-restricted diet versus a calorie-restricted diet on visceral fat and metabolic profiles in women with polycystic ovary syndrome: A randomized controlled trial. Nutrients. 2023; 15 (3): 556. https://doi.org/10.3390/nu15030556
[68]	Jensterle M, Ferjan S, Lezaic L, et al. Semaglutide delays 4-hour gastric emptying in women with polycystic ovary syndrome and obesity. Diabetes Obes Metab.2023; 25(4): 975-984.
[69]	Rudofsky G, Catarin AM, Favre L, et al. Real-world use of once-weekly semaglutide in patients with type 2 diabetes: Results from the SURE Switzerland multicentre, prospective, observational study. Diabetes Res Clin Pract. 2021; 178: 108931. https://doi.org/10.1016/j.diabres.2021.108931
[70]	Rubino D, Abrahamsson N, Davies M, et al. Effect of continued weekly subcutaneous semaglutide vs placeboon weight loss maintenance in adults with overweight or obesity: the STEP 4 randomized clinical trial. J Amer Med Assoc. 2021; 325(14): 1414-1425.
[71]	Carmina E, Longo RA. Semaglutide treatment of excessive body weight in obese PCOS patients unresponsive to lifestyle programs. J Clin Med. 2021; 12(18): 5921.
[72]	Jensterle SM, Ferjan S, Vovk A, et al. Semaglutide reduces fat accumaltion in the tongue: A randomized sinle-blind, pilot study. Diabetes Res Clin Pract. 2021; 2: 178.
[73]	Gadve S, Chavanda S, Gadve S, et al. Oral semaglutide helps in maintaining β-cell function in patients with recent-onset latent autoimmune diabetes in adults: a 6 months prospective study. EndocrinePractice.2024; 30(5): S22-S23.
[74]	Liu M, Guo S, Li X, et al. Semaglutide alleviates ovary inflammation via the AMPK/SIRT1/NK-κB singnaling pathway in polycystic ovary syndrome mice. Drugs Des Devel Ther. 2024; 18:3925-3938. https://doi.org/10.2147/DDT.S484531
[75]	Knop FK, Aroda VR, do Vale RD, et al. Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS1): A randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2023; 402(10403):705-719.
[76]	Jensterle M, Ferjan S, Janez A. The maintenance of long-term weight loss after semalgutide withdrawal in obese women with PCOS treated with metformin: a 2-year observational study. Front Endocrinol. 2024; 15: 13669490.
[77]	Kapitza C, Nosek L, Jensen L, et al. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. J Clin Pharmacol. 2015; 55(5): 497-504.
[78]	Abolghasemi M, Mahjoub S, Esmaeilzadeh S. Serum dipeptidyl peptidase-4 activity and proganulin levels in polycystic ovary syndrome patients. Caspian J Inter Med. 2022; 13(1): 70-75.
[79]	Haidi SS, Nada SZ, Allaq MM. Dipeptidyl peptidase 4 in women with polycystic ovary syndrome. Medical-legal Update. 2020; 20(4): 991-998.
[80]	Kahraman S, Eroglu AA, Elgun S, et al. Serum activities of dipeptidyl peptidase-4 and adenosine deaminase in polycystic ovary syndrome: associated with obesity. Gynecol Endocrinol. 2019; 35(8): 714-718.
[81]	Syabakhash RA, Alwasiti E, Adnan E. Activity of dupeptidyl peptidase-4 (DPP-4) in polycystic ovary syndrome and its association with insulin resistance. Biochem Cell Arch. 2020; 20(1): 1711-1716.
[82]	Devin JK, Nian H, Celedonio JE, et al. Sitagliptin decreases visceral fat and blood glucose in women with polycystic ovarian syndrome. J Clin Endocrinol Metab.2020; 105(1): 136-151.
[83]	Devin, J., Nian, H., Wright, P., & Brown, N. (2019). MON-474 Dipeptidyl Peptidase-4 (DPP4) Inhibition Decreases Visceral Fat and Improves Glucose Metabolism in Overweight Women with Polycystic Ovarian Syndrome. Journal of the Endocrine Society, 3(Suppl 1), MON-474.
[84]	Willard FS, Douros JD, Gabe MBN, et al. Tirzepatide is an imbalanced and bised dual GIP and GLP-1 receptor agonist. 2020; 5(17): e140532. https://doi.org/10.1172/jci.insight.140532
[85]	Buffa R, Polak M, Pearse AGE, et al. Identification of the intestinal cell storing gastric inhibitory peptide. Histochemistry. 1975; 43(3): 249-255.
[86]	Min T, Bain SC. The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2diabetes: te SURPASS clinical trials. Diabetes. 2021; 12(1): 143-157.
[87]	Frías JP, Nauck MA, Van J, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1receptor agonist, in patients with type 2 diabetes: a randomized, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018; 392(10160): 2180-2193
[88]	Rosenstock J, Whysham C, Frías JP, et al. Efficacy and safety of a novel dual GIP and GLP-1receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): A double-blind, randomized, phase 3 trial. Lancet. 2021; 398(10295): 143-155.
[89]	MaoH, Zhang S, Ahmad NN, et al, SURMOUNT- 2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023; 402(10402): 613-626.
[90]	Frias JP, De Block C, Brown K, et al.Tirzapatide improved markers of islet cell function and insulin sensititvity in people with T2D (SURPASS-2). J Clin Endocrinol Metab. 2024; 109(7): 1745-1753.
[91]	Ludvik B, Giorgino F, Jodar E, et al. Once-weekly tirzepatide versus once-daily insulin degludec as add-on to metformin with or whitout SGLT 2 inhibitors in patients with type 2 diabetes (SURPASS-3): A randomised, open-label, parallel-group, phase 3 trial. Lancet. 2021; 398: 583-598.
[92]	Frías JP, Davies MJ, Rosenstock J, et al. Tirzepatide versus semaglutide once weeklyin patients with type 2 diabetes. N Engl J Med. 2021; 385(6): 503-515.
[93]	Sinha R, Papamargaritis D, Sargeant JA, et al. Efficacy and safety of tirzepatide in type 2 diabetes and obesity management. J Obes Metab Syndr. 2023; 32(1): 25-45
[94]	Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022; 387(3): 205-216.
[95]	Wang R, Lin Z, He M, et al. The role of gut microbiota in tirzepatide-mediated alleviation of high-fat diet-induced obesity. Eur J Pharmacol. 2025; 5(1002): 177827.
[96]	Skelley JW, Swearengin K, York AL, et al. The impact of tirzepatide and glucagon-like peptide 1 receptor agonists on oral hormone contraception. J American Pharm Associat. 2024; 64(1): 204-211.
[97]	Anala AD, Saifudeen ISH, Ibrahim M, et al. The potential utility of tirzepatide for the management of polycystic ovary syndrome. J Clin Med. 2023; 12(14): 4575. https://doi.org/10.3390/jcm12144575
[98]	Ferdous J, Hossain MM, Faika MJ, et al. Role of tirzepatide in obesity management among women with polycystic ovary syndrome. Int J Diab Endocrinol. 2025; 10(2): 37-44.
[99]	Mitrovic T, Bjelica A, Petrovic D, et al. Review of current therapeutic approaches for polycystic ovary syndrome. Med Pregl. 2024; 77(9-12): 309-316.
[100]	MinT, BainSC.The role of tirzepatide, dual GIP and GLP-1 receptor agonist, in the management of type 2diabetes: te SURPASS clinical trials. Diabetes. 2021; 12(1): 143-157.

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Medeiros, S. F. D., Yamamoto, M., Jacomeli, J. V., Junior, J. M. S., Maciel, G. A. R., et al. (2026). Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome. Journal of Gynecology and Obstetrics, 14(3), 75-85. https://doi.org/10.11648/j.jgo.20261403.12

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Medeiros, S. F. D.; Yamamoto, M.; Jacomeli, J. V.; Junior, J. M. S.; Maciel, G. A. R., et al. Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome. J. Gynecol. Obstet. 2026, 14(3), 75-85. doi: 10.11648/j.jgo.20261403.12

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Medeiros SFD, Yamamoto M, Jacomeli JV, Junior JMS, Maciel GAR, et al. Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome. J Gynecol Obstet. 2026;14(3):75-85. doi: 10.11648/j.jgo.20261403.12

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@article{10.11648/j.jgo.20261403.12,
  author = {Sebastião Freitas de Medeiros and MárciaMarlyWinck Yamamoto and JamillyAparecida Vicente Jacomeli and José Maria Soares Junior and Gustavo Arantes Rosa Maciel and Edmund Chada Baracat},
  title = {Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome},
  journal = {Journal of Gynecology and Obstetrics},
  volume = {14},
  number = {3},
  pages = {75-85},
  doi = {10.11648/j.jgo.20261403.12},
  url = {https://doi.org/10.11648/j.jgo.20261403.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jgo.20261403.12},
  abstract = {This comprehensive review focuses on the relevance of hyperinsulinemia in women with polycystic ovary syndrome (PCOS). It highlights the most robust scientific evidence on the management of this condition within the context of PCOS. A systematic search of studies published in English language was conducted using Google Scholar, PubMed, and Cochrane databases. Keywords used alone or combined with “PCOS” included: hyperinsulinemia, incretin hormones, and dipeptidyl peptidase-4. The search strategy was complemented by manual review of references from selected articles. Glucagon-like peptide-1 receptor agonist and glucagon-dependent insulin tropic polypeptide provide various metabolic beneficial effects in addition to the weight loss. Dipeptidyl peptidase-4 inhibitors, expressed by various cells, prevent GLP-1 degradation and decreases insulin signaling in different cells, particularly in hepatocytes, and adipocytes. Regarding the management of hyperinsulinemia, the review suggests that incretin hormone agonist and dipeptidyl peptidase-4 inhibitors may represent favorable therapeutic options for addressing insulin resistance in women with PCOS, particularly those with obesity. However, this review does not explore dietary interventions and physical activity as primary strategies for managing dysglycemia in this population.},
 year = {2026}
}

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TY  - JOUR
T1  - Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome
AU  - Sebastião Freitas de Medeiros
AU  - MárciaMarlyWinck Yamamoto
AU  - JamillyAparecida Vicente Jacomeli
AU  - José Maria Soares Junior
AU  - Gustavo Arantes Rosa Maciel
AU  - Edmund Chada Baracat
Y1  - 2026/07/11
PY  - 2026
N1  - https://doi.org/10.11648/j.jgo.20261403.12
DO  - 10.11648/j.jgo.20261403.12
T2  - Journal of Gynecology and Obstetrics
JF  - Journal of Gynecology and Obstetrics
JO  - Journal of Gynecology and Obstetrics
SP  - 75
EP  - 85
PB  - Science Publishing Group
SN  - 2376-7820
UR  - https://doi.org/10.11648/j.jgo.20261403.12
AB  - This comprehensive review focuses on the relevance of hyperinsulinemia in women with polycystic ovary syndrome (PCOS). It highlights the most robust scientific evidence on the management of this condition within the context of PCOS. A systematic search of studies published in English language was conducted using Google Scholar, PubMed, and Cochrane databases. Keywords used alone or combined with “PCOS” included: hyperinsulinemia, incretin hormones, and dipeptidyl peptidase-4. The search strategy was complemented by manual review of references from selected articles. Glucagon-like peptide-1 receptor agonist and glucagon-dependent insulin tropic polypeptide provide various metabolic beneficial effects in addition to the weight loss. Dipeptidyl peptidase-4 inhibitors, expressed by various cells, prevent GLP-1 degradation and decreases insulin signaling in different cells, particularly in hepatocytes, and adipocytes. Regarding the management of hyperinsulinemia, the review suggests that incretin hormone agonist and dipeptidyl peptidase-4 inhibitors may represent favorable therapeutic options for addressing insulin resistance in women with PCOS, particularly those with obesity. However, this review does not explore dietary interventions and physical activity as primary strategies for managing dysglycemia in this population.
VL  - 14
IS  - 3
ER  -

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Sebastião Freitas de Medeiros

Department of Gynecology and Obstetrics, Federal University of Mato-Grosso, Cuiabá, Brazil;Tropical Institute of Reproductive Medicine, Cuiabá, Brazil

Contact Email

http://orcid.org/0000-0003-1292-2515
MárciaMarlyWinck Yamamoto

Tropical Institute of Reproductive Medicine, Cuiabá, Brazil

http://orcid.org/0000-0002-4845-4226
JamillyAparecida Vicente Jacomeli

Tropical Institute of Reproductive Medicine, Cuiabá, Brazil

http://orcid.org/0009-0009-8309-6952
José Maria Soares Junior

Department of Gynecology and Obstetrics, University of São Paulo, São Paulo, Brazil

http://orcid.org/0000-0003-0774-9404
Gustavo Arantes Rosa Maciel

Department of Gynecology and Obstetrics, University of São Paulo, São Paulo, Brazil

http://orcid.org/0000-0001-9097-8528
Edmund Chada Baracat

Department of Gynecology and Obstetrics, University of São Paulo, São Paulo, Brazil

http://orcid.org/0000-0003-0111-9030

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Medeiros, S. F. D., Yamamoto, M., Jacomeli, J. V., Junior, J. M. S., Maciel, G. A. R., et al. (2026). Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome. Journal of Gynecology and Obstetrics, 14(3), 75-85. https://doi.org/10.11648/j.jgo.20261403.12

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ACS Style

Medeiros, S. F. D.; Yamamoto, M.; Jacomeli, J. V.; Junior, J. M. S.; Maciel, G. A. R., et al. Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome. J. Gynecol. Obstet. 2026, 14(3), 75-85. doi: 10.11648/j.jgo.20261403.12

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AMA Style

Medeiros SFD, Yamamoto M, Jacomeli JV, Junior JMS, Maciel GAR, et al. Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome. J Gynecol Obstet. 2026;14(3):75-85. doi: 10.11648/j.jgo.20261403.12

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@article{10.11648/j.jgo.20261403.12,
  author = {Sebastião Freitas de Medeiros and MárciaMarlyWinck Yamamoto and JamillyAparecida Vicente Jacomeli and José Maria Soares Junior and Gustavo Arantes Rosa Maciel and Edmund Chada Baracat},
  title = {Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome},
  journal = {Journal of Gynecology and Obstetrics},
  volume = {14},
  number = {3},
  pages = {75-85},
  doi = {10.11648/j.jgo.20261403.12},
  url = {https://doi.org/10.11648/j.jgo.20261403.12},
  eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.jgo.20261403.12},
  abstract = {This comprehensive review focuses on the relevance of hyperinsulinemia in women with polycystic ovary syndrome (PCOS). It highlights the most robust scientific evidence on the management of this condition within the context of PCOS. A systematic search of studies published in English language was conducted using Google Scholar, PubMed, and Cochrane databases. Keywords used alone or combined with “PCOS” included: hyperinsulinemia, incretin hormones, and dipeptidyl peptidase-4. The search strategy was complemented by manual review of references from selected articles. Glucagon-like peptide-1 receptor agonist and glucagon-dependent insulin tropic polypeptide provide various metabolic beneficial effects in addition to the weight loss. Dipeptidyl peptidase-4 inhibitors, expressed by various cells, prevent GLP-1 degradation and decreases insulin signaling in different cells, particularly in hepatocytes, and adipocytes. Regarding the management of hyperinsulinemia, the review suggests that incretin hormone agonist and dipeptidyl peptidase-4 inhibitors may represent favorable therapeutic options for addressing insulin resistance in women with PCOS, particularly those with obesity. However, this review does not explore dietary interventions and physical activity as primary strategies for managing dysglycemia in this population.},
 year = {2026}
}

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TY  - JOUR
T1  - Exploring on the Hyperinsulinism Management in Women with Polycystic Ovary Syndrome
AU  - Sebastião Freitas de Medeiros
AU  - MárciaMarlyWinck Yamamoto
AU  - JamillyAparecida Vicente Jacomeli
AU  - José Maria Soares Junior
AU  - Gustavo Arantes Rosa Maciel
AU  - Edmund Chada Baracat
Y1  - 2026/07/11
PY  - 2026
N1  - https://doi.org/10.11648/j.jgo.20261403.12
DO  - 10.11648/j.jgo.20261403.12
T2  - Journal of Gynecology and Obstetrics
JF  - Journal of Gynecology and Obstetrics
JO  - Journal of Gynecology and Obstetrics
SP  - 75
EP  - 85
PB  - Science Publishing Group
SN  - 2376-7820
UR  - https://doi.org/10.11648/j.jgo.20261403.12
AB  - This comprehensive review focuses on the relevance of hyperinsulinemia in women with polycystic ovary syndrome (PCOS). It highlights the most robust scientific evidence on the management of this condition within the context of PCOS. A systematic search of studies published in English language was conducted using Google Scholar, PubMed, and Cochrane databases. Keywords used alone or combined with “PCOS” included: hyperinsulinemia, incretin hormones, and dipeptidyl peptidase-4. The search strategy was complemented by manual review of references from selected articles. Glucagon-like peptide-1 receptor agonist and glucagon-dependent insulin tropic polypeptide provide various metabolic beneficial effects in addition to the weight loss. Dipeptidyl peptidase-4 inhibitors, expressed by various cells, prevent GLP-1 degradation and decreases insulin signaling in different cells, particularly in hepatocytes, and adipocytes. Regarding the management of hyperinsulinemia, the review suggests that incretin hormone agonist and dipeptidyl peptidase-4 inhibitors may represent favorable therapeutic options for addressing insulin resistance in women with PCOS, particularly those with obesity. However, this review does not explore dietary interventions and physical activity as primary strategies for managing dysglycemia in this population.
VL  - 14
IS  - 3
ER  -

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